Lung cancer

Is it time to take a step back to take the next step forward?

Thursday, 6 Dec 2018


It’s an optimistic time for non-small cell lung cancer (NSCLC) treatment. Within the last few years, the pipeline of available therapies and tests has boomed which has changed not only the outlook, but the way medicine is performed in this area. To reflect on how clinicians are managing patients with NSCLC has changed and consider where it is going, the limbic spoke with Professor Stephen Clarke. He is a medical oncologist, pharmacologist and translational researcher at the Northern Cancer Institute and Royal North Shore Hospital, Director of Cancer Services at Northern Sydney Local Health District and Professor of Medicine at the University of Sydney.

Reassessing where we are now in NSCLC

“Describing the typical patient is in reality more complex than many people might think. It depends on where you are, as the types and volume of patients you see is known to differ greatly by local health districts (LHDs) ” notes Prof. Clarke.

As Prof. Clarke highlighted, the incidence and mortality of patients with lung cancer varies across Australia – even down to the LHD level. This is thought to be primarily driven by three factors: geographical location, socioeconomic status and Indigenous status of the patient. A 2013 Cancer Australia report found the incidence of lung cancer tended to increase with increasing remoteness for men (but not women), decreased with improving socioeconomic status and was 1.6-1.7 times higher in Indigenous than non-Indigenous Australians.1,2 Professor Clarke notes that this is in line with what we are still seeing today in practice. “When the socioeconomic status is lower than average, there tends to be a higher rate of smokers, and these are the typical, older patients most people think of when they think of lung cancer. In more affluent areas the smoking rate is lower, but we can still see cases of mutation-driven NSCLC. In our LHD, we are seeing a fair few cases of younger (middle aged), Asian females presenting with mutated cancers. One challenge I think we face is the inconsistent access to early mutation testing – and given the more personalised approach to treatment this is definitely an area that could be worked on.”1,2

Earlier diagnosis and testing are not new demands from the health community treating patients with NSCLC. The latest data from the Australian Cancer Database and the Australian Institute of Health and Welfare from 2011 showed the vast majority (~70%) of all patients with NSCLC were presenting with Stage IV or ‘unknown’ cancer.3 This meant that with higher-stages tumours, clinicians were simply deciding whether they could resect the tumour or not, and then which cocktail of chemotherapy might the patient tolerate best. Now, with more treatments available things have become more complex for clinicians, particularly medical oncologists. Professor Clarke explains, “unlike before, where we had few choices and few patients who were resectable, with a pipeline newer therapies we will likely have to not only consider how we can prolong life for these patients, but also the opportunity to potentially offer quality of life. For some who would have not been considered resectable before might have a chance to be resectable, and for those that do progress, we now have multiple lines of therapy we can consider – giving them and us hope that did not exist before now. One of the biggest challenges we clinicians face now is choice – given that clinical trials have been designed to examine the effectiveness of treatments compared with standard of care chemotherapy, it can be a challenge to decide on which therapy to use, in what sequence and in which patients.”4,5

Looking forward to where we want to be

Where all clinicians and patients want to be is at a stage where NSCLC becomes a mostly curable disease, but we are not there just yet. However, where we are today is in a position where patients can expect longer progression-free survival and overall survival with small-molecule inhibitors like the tyrosine kinase inhibitors (TKIs) and immunotherapies than with traditional chemotherapy regimens.5 However, as Prof. Clarke explains, it is not just about the clinical endpoints we see in trials, it’s also about always planning for the next step. “It’s a given that patients want to live longer, and one of the hardest parts of my job is getting to that point where we’ve run out of options for them. That’s why it is so important to map out the best treatment plan that meets each individual’s needs. Unfortunately, that’s not an easy task these days with so many treatments and a growing diversity of patients. It is a rapidly evolving space that adds another dimension of challenge to our already busy workloads. Finding a way to merge the collective experiences will likely help us get there.”

Making sure we’ll get there – taking the first steps

Given an emphasis on access to treatments based on Stage of NSCLC, first and foremost Prof. Clarke suggests getting patients screened as early and thoroughly as possible could make a big impact on the future of NSCLC. “Ensuring our networks of General Practitioners and the general public are aware of the risks and signs of lung cancer is fundamental to diagnosing the cancer as early as possible.”

Secondly, once we have the patient in clinic, streamlined, rapid processing of patients to ensure they are evaluated in tertiary care quickly could help shave crucial weeks off delays in access to treatment. “Access to care once in the lung clinics can vary considerably between LHDs and of course between the States and Territories.1,2 By understanding each other’s systems, we might be able to take the best of each setting to create the ultimate patient pathway,” suggests Prof. Clarke.

Thirdly, a clear map of which regimens to use, and in which sequence is necessary to get the most out of the treatments available. Prof. Clarke explains, “clinical trial evidence only gets us so far, we’ll probably need to start looking at the emerging real-world evidence as well to see how the combinations and permutations perform in practice. The reality is, not everyone will have had experience with all of the agents currently available (or to come). In an ideal world, clinicians will form collaborations that facilitate the sharing of knowledge and the determination of treatment guidelines as more evidence emerges.”

Sequencing of the new therapies is going to be important to maximise the potential treatment pathway for patients. For example, looking at the TKIs crizotinib and alectinib, emerging real-world evidence may help clinicians in sequence decisions.6 A small retrospective analysis of medical records of patients treated with crizotinib followed by alectinib found that although alectinib had a progression-free survival (PFS) of 15.2 months (range 1.0-28.3) compared with 6.1 months (range 1.0-15.4) for patients treated with crizotinib first, the overall survival was 51.1 months (range 20.9-69.5) from the diagnosis of metastatic disease and 48.6 months (range 19.8-50.1) from the initiation of crizotinib treatment. A larger analysis of French expanded access program participants found a similar trend.7 The collection of more real-world data may help in understanding these interactions as clinical trials do not always provide evidence on every angle.

Professor Clarke’s considerations for the future of NSCLC in Australia

  1. Earlier diagnosis and phenotyping of patients.
  2. Streamlining access to treatment.
  3. Collecting and sharing real-world evidence to help form guidelines on the sequencing of therapies.

While the horizon is likely to get even more complex as more options become available, the first step is understanding all the place of all the therapies amongst a growing and diverse patient population. Professor Clarke concludes, “routine is a word that can come with a lot of stigma – of being boring or not progressive, however, routine is what we oncologists are striving for in this space that is just waiting for enough data to make sense of the complexity we face on a daily basis.”

 

This article was sponsored by Pfizer, which has no control over editorial content. The content is entirely independent and based on published studies and experts’ opinions, the views expressed are not necessarily those of Pfizer.

References:

  1. Cancer Australia. Best practice approaches to lung cancer care – A review of the literature. Cancer Australia, Surry Hills, NSW,(2013).
  2. Australian Government. Cancer Australia. Cancer incidence. Available at: https://ncci.canceraustralia.gov.au/diagnosis/cancer-incidence/cancer-incidence (accessed 21 September 2018).
  3. Australian Government. Cancer Australia. Distribution of cancer stage. Available at: https://ncci.canceraustralia.gov.au/diagnosis/distribution-cancer-stage/distribution-cancer-stage (accessed 21 September 2018).
  4. Australian Government. Cancer Australia. Lung cancer. Treatment options. Available at: https://lung-cancer.canceraustralia.gov.au/treatment (accessed 21 September 2018).
  5. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Non-small cell lung cancer. Version 4.2018.
  6. Watanabe S et al. Clin Lung Cancer 2016;17(6):528-534.
  7. Duruisseaux M et al. Oncotarget 2017;8(13):21903-21917.

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